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2009
Conference Paper
Titel
Sound oral to inhalation extrapolation factors for human health risk assessment
Titel Supplements
Abstract
Abstract
Route-to-route extrapolation factors (EF) are commonly used in regulatory toxicology for risk assessment of substances for which no data on the relevant exposure route are available. As most animal studies on chronic toxicity use oral application, route-to-route assessment factors are needed to extrapolate from oral to inhalation or to dermal exposure. So far, route-to-route extrapolation is restricted to substances with comparable toxicity in the contemplated routes ([Kalberlah and Schneider, 1998] and Wilschut et al., 1998 Wilschut, Hakkert, Bos, Stevenson, 1998. Evaluation of route-to-route extrapolation in health risk assessment for dermal and respiratory exposure chemiclas. TNO Report No. V97520.[Wilschut et al., 1998]). Kinetics, critical toxic effect and metabolism of the systemically active substance have to be similar for both routes. However, often such information is not available, or has to be predicted according to e.g. structural or physico-chemical properties. Thus, there is a need to derive general extrapolation factors and to specify additional extrapolation factors for certain classes of substances. Already several route-to-route EFs are described based on limited datasets ([Vermeire et al., 2001] and [Evans et al., 2001]). We describe the derivation of oral-to-inhalation EFs using the database RepDose. Currently RepDose contains about 581 chemicals, and 1706 studies on subacute to chronic toxicity. The high quality and amount of data in RepDose allows to determine oral-to-inhalation EFs using a tiered approach, starting with all available information and restricting the analysis to chemicals with studies on one species and subsequently one exposure duration. Without any knowledge on the substance and its properties i.e. including also irritating compounds a median oral-to-inhalation EF of 2 is derived. We demonstrate that this general EF can be modified for defined classes of compounds by taking structural and/or physico-chemical properties into account.